BACKGROUND: The early stages of tumor bone metastasis are closely associated with changes in the vascular niche of the bone microenvironment, and abnormal angiogenesis accelerates tumor metastasis and progression. However, the effects of lung adenocarcinoma (LUAD) cells reprogrammed by the bone microenvironment on the vascular niche within the bone microenvironment and the underlying mechanisms remain unclear. This study investigates the effects and mechanisms of LUAD cells reprogrammed by the bone microenvironment on endothelial cells and angiogenesis, providing insights into the influence of tumor cells on the vascular niche within the bone microenvironment. METHODS: The culture media from bone-metastatic LUAD cell A549-GFP-LUC-BM3 (BM3-CM) and A549-GFP-LUC (A549-CM) were separately applied to human umbilical vein endothelial cell (HUVEC). A colony formation assay, scratch assay, and tube formation assay were conducted to evaluate the proliferation, migration, and angiogenesis of HUVEC. Gene set enrichment analysis (GSEA) was conducted to identify enriched pathways, while reverse transcription quantitative polymerase chain reaction (RT-qPCR) and enzyme linked immunosorbent assay (ELISA) were performed to quantify hepatocyte growth factor (HGF), a protein that plays a crucial role in angiogenesis. Furthermore, the pivotal function of HGF and its underlying molecular mechanisms have been substantiated through the utilisation of recombinant proteins, neutralising antibodies, pathway inhibitors, immunofluorescence staining, and Western blot. RESULTS: BM3-CM demonstrated a more pronounced impact on the proliferation, migration, and angiogenesis of HUVEC compared to A549-CM. Bioinformatics analysis, combined with in vitro experiment, demonstrated that the secretory protein HGF was significantly elevated in BM3 cells and BM3-CM (P<0.05). The addition of HGF neutralizing antibodies to BM3-CM inhibited the promoting effect of BM3-CM on HUVEC (P<0.05), while the addition of recombinant HGF to A549-CM reproduced that promoting effect of BM3-CM on HUVEC (P<0.05). HGF can enhance the activation of YAP (Yes-associated protein) in HUVEC, and this promotion effect may be achieved by activating Src and activating YAP into the nucleus (P<0.05), but this effect can be inhibited by HGF neutralizing antibodies (P<0.05). Furthermore, the addition of recombinant HGF to A549-CM can recapitulate the YAP activation effect of BM3-CM in HUVEC (P<0.05). CONCLUSIONS Bone microenvironment reprogrammed bone-metastatic LUAD cells BM3 promote the proliferation, migration, and angiogenesis of HUVEC through the HGF/YAP axis, potentially playing a significant role in the modifications of the vascular niche.
Humans ; Hepatocyte Growth Factor/genetics* ; Signal Transduction ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells ; Bone Neoplasms/blood supply* ; Adenocarcinoma of Lung/genetics* ; Adaptor Proteins, Signal Transducing/genetics* ; Lung Neoplasms/genetics* ; Cell Movement ; Cell Proliferation ; YAP-Signaling Proteins ; Transcription Factors/genetics* ; Cell Line, Tumor ; Tumor Microenvironment ; Angiogenesis

Objective: To investigate the predictive value of D-dimer for deep venous thrombosis (DVT) of lower extremity in adult burn patients. Methods: A retrospective case series study was conducted. The clinical data of 3 861 adult burn patients who met the inclusion criteria and were admitted to the Department of Burns of Zhengzhou First People's Hospital from January 1, 2015 to December 31, 2019 were collected. The patients were divided into DVT group (n=77) and non-DVT group (n=3 784) according to whether DVT of lower extremity occurred during hospitalization or not. Data of patients in the two groups were collected and compared, including the gender, age, total burn area, D-dimer level, with lower limb burn and inhalation injury or not on admission, with sepsis/septic shock, femoral vein indwelling central venous catheter (CVC), history of surgery, and infusion of concentrated red blood cells or not during hospitalization. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, and chi-square test. The indicators with statistically significant differences between the two groups were analyzed with multivariate logistic regression analysis to screen the independent risk factors for DVT of lower extremity in 3 861 adult burn patients. The receiver operating characteristic (ROC) curve of the independent risk factors predicting DVT of lower extremity in 3 861 adult burn patients were drawn, and the area under the curve (AUC), the optimal threshold value, and the sensitivity and specificity under the optimal threshold value were calculated. The quality of the AUC was compared by Delong test, and the sensitivity and specificity under the optimal threshold value were compared using chi-square test. Results: There were no statistically significant differences in gender, occurrence of sepsis/septic shock or history of surgery during hospitalization between patients in the two groups (P>0.05), while there were statistically significant differences in age, total burn area, D-dimer level, lower limb burn and inhalation injury on admission, and femoral vein indwelling CVC and infusion of concentrated red blood cells during hospitalization between patients in the two groups (t=-8.17, with Z values of -5.04 and -10.83, respectively, χ² values of 21.83, 5.37, 7.75, and 4.52, respectively, P<0.05 or P<0.01). Multivariate logistic regression analysis showed that age, total burn area, and D-dimer level were the independent risk factors for DVT of lower extremity in 3 861 adult burn patients (with odds ratios of 1.05, 1.02, and 1.14, respectively, 95% confidence intervals of 1.04-1.06, 1.00-1.03, and 1.10-1.20, respectively, P<0.05 or P<0.01). The AUCs of ROC of age, total burn area, and D-dimer level for predicting DVT of lower extremity in 3 861 adult burn patients were 0.74, 0.67, and 0.86, respectively (with 95% confidence intervals of 0.68-0.80, 0.60-0.74, and 0.83-0.89, respectively, P values<0.01), the optimal threshold values were 50.5 years old, 10.5% total body surface area, and 1.845 mg/L, respectively, the sensitivity under the optimal threshold values were 71.4%, 70.1%, and 87.0%, respectively, and the specificity under the optimal threshold values were 66.8%, 67.2%, and 72.9%, respectively. The AUC quality and sensitivity and specificity under the optimal threshold value of D-dimer level were significantly better than those of age (z=3.29, with χ² values of 284.91 and 34.25, respectively, P<0.01) and total burn area (z=4.98, with χ² values of 326.79 and 29.88, respectively, P<0.01), while the AUC quality and sensitivity and specificity under the optimal threshold values were similar between age and total burn area (P>0.05). Conclusions: D-dimer level is an independent risk factor for DVT of lower extremity in adult burn patients, its AUC quality and sensitivity and specificity under the optimal threshold value are better than those of age and total burn area, and it has good predictive value for DVT of lower extremity in adult burn patients.
Adult ; Burns/complications* ; Fibrin Fibrinogen Degradation Products/analysis* ; Humans ; Lower Extremity/blood supply* ; Lung Injury/etiology* ; Middle Aged ; Prognosis ; Retrospective Studies ; Shock, Septic/etiology* ; Venous Thrombosis/etiology*

BACKGROUND: The aim of this study was to analyze the incidence of lower limb deep venous thrombosis (DVT) and the corresponding coagulation status in severe patients after thoracic surgery. METHODS: Severe patients after thoracic surgery who received mechanical prophylaxis of lower limb DVT between July 2016 and June 2018 were analysed retrospectively. Their general information, disease species, surgical treatment, and coagulation index were reviewed. RESULTS: Fifty patients were finally included. There were 34 male and 16 female, aging from 22 to 80 years. The incidence of DVT was 22.0%, all of them were isolated calf DVT. The incidence was 29.4% in male patients, while 6.3% in female; 23.5% in malignant diseases and 18.6% in benign. All coagulation index presented no statistical difference between patients with and without DVT, except activated partial thromboplastin time (APTT). CONCLUSIONS Even on the basis of adequate mechanical prophylaxis, lower limb DVT is common in severe patients after thoracic surgery. Meanwhile, male patients and malignant diseases are more suscepted.
Adult ; Aged ; Aged, 80 and over ; Blood Coagulation ; Female ; Humans ; Incidence ; Lower Extremity ; blood supply ; Lung Neoplasms ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Thoracic Surgical Procedures ; adverse effects ; Venous Thrombosis ; etiology ; physiopathology ; Young Adult

Angiogenesis Inhibitors ; pharmacology ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; blood supply ; pathology ; Humans ; Lung Neoplasms ; blood supply ; pathology ; Neovascularization, Pathologic ; drug therapy ; therapy ; Societies, Medical

OBJECTIVETo explore the expression of CASZ1 and its relationship with the pulmonary microvascular development in lung tissue of newborn rats exposed to hyperoxia which induced bronchopulmonary dysplasia (BPD).

METHODForty-eight newborn Sprague Dawley(SD) rats (male and female unlimited) were randomly divided into two groups: experimental group and control group according to random digits table with 24 in each.The rats in experimental group were exposed to high oxygen volume fraction of 800 ml/L and the rats in control group were exposed to normal air. Eight rats were randomly selected from each group on day 3 and 7 after oxygen exposure.The sections of lung were stained with HE method in order to assess lung histological changes, the alveolar development was evaluated by the number of radial alveolar count (RAC) and septal wall thickness. CD31 was detected by immunohistochemistry (IHC) method and the capillary density was calculated. The location, distribution and expression of CASZ1 in the lung tissue were detected by the immunohistochemistry, Western blotting, and quantitative PCR (qPCR).

RESULT(1) Stained by HE, lungs of experimental group showed destroyed alveoli, alveoli fusion and increased septal wall thickness, RAC were significantly lower than those in control group(14 d: septal wall thickness (12.69 ± 0.63) μm vs. (6.53 ± 0.16) μm, RAC 5.9 ± 0.4 vs. 8.4 ± 1.0, t = 19.046, 4.760, P both = 0.000). (2) CD31 protein was expressed predominantly in cytoplasm of pulmonary microvascular endothelial cells. The experimental group CD31 average optical density (AIOD) were decreased compared with control group((16.6 ± 1.6) × 10(3) vs.(40.1 ± 2.4) × 10(3), (18.1 ± 1.4) × 10(3) vs.(83.2 ± 5.2) × 10(3), (49.2 ± 5.4) × 10(3) vs.(136.2 ± 28.1) × 10(3), t=16.185, 16.066 and 6.078, P<0.01 for all comparisons). Capillary density in experimental group was also significantly decreased compared with control group ((3.84 ± 0.15)% vs.(6.01 ± 0.22)%, (4.17 ± 0.38)% vs.(6.15 ± 0.24)%, (5.43 ± 0.44)% vs. (9.13 ± 0.25)%, t = 16.124, 8.773 and 14.076, P all < 0.01). (3)RT-qPCR and Western blotting showed that the CASZ1 mRNA significantly increased in experimental group compared with control group(0.56 ± 0.17 vs. 1.00 ± 0.26, 0.32 ± 0.29 vs. 0.58 ± 0.14, 0.14 ± 0.22 vs. 0.56 ± 0.15, t=3.890, 3.303 and 2.388, P < 0.05 for all comparisons), and the protein expression of CASZ1 also significantly increased in experimental group compared with control group (0.65 ± 0.02 vs. 0.78 ± 0.23, 0.46 ± 0.03 vs. 0.75 ± 0.05, 0.34 ± 0.22 vs. 0.75 ± 0.04, t=6.200 and 10.485 and 14.998, P < 0.05 for all comparisons). (4)The protein level of CASZ1 in experimental group was positively correlated with capillary density (r=0.519, P<0.01).

CONCLUSIONCASZ1 is involved in the whole process of newborn rats BPD and may be linked to pulmonary microvascular dysplasia.

Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; pathology ; Female ; Hyperoxia ; pathology ; Lung ; blood supply ; pathology ; Male ; Oxygen ; adverse effects ; Pulmonary Alveoli ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Transcription Factors ; metabolism

OBJECTIVETo study the clinical value of three-dimensional (3D) reconstruction of the lung and its vasculature in virtual surgery for lung cancer.

METHODSFrom May 2015 to August 2015, 24 patients with non-small cell lung cancer underwent surgical treatment in our department. The patients were randomly divided into experimental and control groups (12 in each group). For the patients in the experimental group, 3D models were reconstructed by surface rendering based on thoracic CT scanning data using Mimics software on a personal computer, and manipulations of the structures were simulated on the models before the operation. For the patients in the control group, surgeries were performed according to the conventional scheme. The operation time, blood loss and postoperative hospital stay were compared between the two groups.

RESULTSThe 3D models of lung cancer consisting of the thoracic bone, lungs, tumor, tracheobronchial tree, and pulmonary vessels were reconstructed successfully. The models had highly geometrical similarity and offered excellent 3D view of the morphological characteristics of the tumor and the spatial relationship between the adjacent structures. The models allowed editing and provided vivid view during the simulated operation of tumor excision to facilitate individualized surgical planning and reduce the surgery risks. All the patients underwent tumor resection smoothly without perioperative death or incidences of postoperative hemorrhage or infection. The operation time was significantly shorter in the experimental group than in the control group (P<0.05) but the blood loss and postoperative hospital stay were comparable between the two groups.

CONCLUSIONThe individualized lung cancer modeling can facilitate the evaluation of preoperative risks and allows for more accurate surgical planning.

Carcinoma, Non-Small-Cell Lung ; blood supply ; surgery ; Humans ; Imaging, Three-Dimensional ; Lung Neoplasms ; blood supply ; surgery ; Models, Anatomic ; Operative Time ; Software ; Tomography, X-Ray Computed

OBJECTIVETo appraise the significance of extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), and intrathoracic blood volume index (ITBVI) in the differential diagnosis of the type of burn-induced pulmonary edema.

METHODSThe clinical data of 38 patients, with severe burn hospitalized in our burn ICU from December 2011 to September 2014 suffering from the complication of pulmonary edema within one week post burn and treated with mechanical ventilation accompanied by pulse contour cardiac output monitoring, were retrospectively analyzed. The patients were divided into lung injury group ( L, n = 17) and hydrostatic group (H, n = 21) according to the diagnosis of pulmonary edema. EVLWI, PVPI, ITBVI, oxygenation index, and lung injury score ( LIS) were compared between two groups, and the correlations among the former four indexes and the correlations between each of the former three indexes and types of pulmonary edema were analyzed. Data were processed with t test, chi-square test, Mann-Whitney U test, Pearson correlation test, and accuracy test [receiver operating characteristic (ROC) curve].

RESULTSThere was no statistically significant difference in EVLWI between group L and group H, respectively (12.9 ± 3.1) and (12.1 ± 2.1) mL/kg, U = 159.5, P > 0.05. The PVPI and LIS of patients in group L were respectively 2.6 ± 0.5 and (2.1 ± 0.6) points, and they were significantly higher than those in group H [1.4 ± 0.3 and (1.0 ± 0.6) points, with U values respectively 4.5 and 36.5, P values below 0.01]. The ITBVI and oxygenation index of patients in group L were respectively (911 197) mL/m2 and (136 ± 69) mmHg (1 mmHg = 0.133 kPa), which were significantly lower than those in group H [(1,305 ± 168) mL/m2 and (212 ± 60) mmHg, with U values respectively 21.5 and 70.5, P values below 0.01]. In group L, there was obviously positive correlation between EVLWI and PVPI, or EVLWI and ITBVI (with r values respectively 0.553 and 0.807, P < 0.05 or P < 0.01), and there was obviously negative correlation between oxygenation index and EVLWI, or oxygenation index and PVPI (with r values respectively -0.674 and -0.817, P values below 0.01). In group H, there was obviously positive correlation between EVLWI and ITBVI (r = 0.751, P < 0.01) but no obvious correlation between EVLWI and PVPI, oxygenation index and EVLWI, or oxygenation index and PVPI (with r values respectively -0.275, 0.197, and 0:062, P values above 0.05). The total area under ROC curve of PVPI value for differentiating the type of pulmonary edema was 0.987 [with 95% confidence interval (CI) 0.962-1.013, P < 0.01], and 1.9 was the cutoff value with sensitivity of 94.1% and specificity of 95.2% . The total area under ROC curve of ITBVI value for differentiating the type of pulmonary edema was 0.940 (with 95% CI 0.860-1.020, P < 0.01), and 1,077. 5 mL/m2 was the cutoff value with sensitivity of 95.2% and specificity of 88.2%.

CONCLUSIONSEVLWI, PVPI, and ITBVI have an important significance in the differential diagnosis of the type of burn-induced pulmonary edema, and they may be helpful in the early diagnosis and management of burn-induced pulmonary edema.

Blood Gas Analysis ; Blood Volume ; Burns ; complications ; Capillary Permeability ; Diagnosis, Differential ; Extravascular Lung Water ; Humans ; Lung ; blood supply ; Lung Injury ; physiopathology ; therapy ; Monitoring, Physiologic ; Pulmonary Edema ; diagnosis ; etiology ; ROC Curve ; Respiration, Artificial ; Retrospective Studies

The effect of high frequency oscillatory ventilation (HFOV) at early stage on hemodynamic parameters, extravascular lung water (EVLW), lung capillary permeability, CC16 and sICAM-1 in piglets with pulmonary or extrapulmonary acute respiratory distress syndrome (ARDS) was explored. Central vein pressure (CVP) and pulse indicator continuous cardiac output (PiCCO) were monitored in 12 anesthetized and intubated healthy piglets. Pulmonary ARDS (ARDSp) and extrapulmonary ARDS (ARDSexp) models were respectively established by lung lavage of saline solution and intravenous injection of oleic acid. Then the piglets received HFOV for 4 h. EVLW index (EVLWI), EVLW/intratroracic blood volume (ITBV) and pulmonary vascular permeability index (PVPI) were measured before and after modeling (T0 and T1), and T2 (1 h), T3 (2 h), T4 (3 h) and T5 (4 h) after HFOV. CC16 and sICAM-1 were also detected at T1 and T5. Results showed at T1, T3, T4 and T5, EVLWI was increased more significantly in ARDSp group than in ARDSexp group (P<0.05). The EVLWI in ARDSp group was increased at T1 (P=0.008), and sustained continuously within 2 h (P=0.679, P=0.216), but decreased at T4 (P=0.007) and T5 (P=0.037). The EVLWI in ARDSexp group was also increased at T1 (P=0.003), but significantly decreased at T3 (P=0.002) and T4 (P=0.019). PVPI was increased after modeling in both two groups (P=0.004, P=0.012), but there was no significant change within 4 h (T5) under HFOV in ARDSp group, while PVPI showed the increasing trends at first, then decreased in ARDSexp group after HFOV. The changes of EVLW/ITBV were similar to those of PVPI. No significant differences were found in ΔEVLWI (P=0.13), ΔPVPI (P=0.28) and ΔEVLW/ITBV between the two groups (P=0.63). The significant decreases in both CC16 and sICAM-1 were found in both two groups 4 h after HFOV, but there was no significant difference between the two groups. It was concluded that EVLWI and lung capillary permeability were markedly increased in ARDSp and ARDSexp groups. EVLW could be decreased 4 h after the HFOV treatment. HFOV, EVLW/ITBV and PVPI were increased slightly at first, and then decreased in ARDSexp group, while in ARDSp group no significant difference was found after modeling. No significant differences were found in the decreases in EVLW and lung capillary permeability 4 h after HFOV.
Animals ; Capillaries ; physiopathology ; High-Frequency Ventilation ; Lung ; blood supply ; Respiratory Distress Syndrome, Adult ; physiopathology ; Swine

PURPOSE: Anastomotic airway complications are a major cause of morbidity and mortality after lung transplantation (LTx). In this study, the authors identified types and clinical outcomes of airway complications after LTx. MATERIALS AND METHODS: All bronchial anastomotic complications were analyzed in a total of 94 LTx cases involving 90 recipients who underwent surgery between July 2006 and May 2014. Fifteen LTx cases (14 recipients) with incomplete medical records for fiberoptic bronchoscopy (FBS) and three cases underwent heart-lung transplantation (HLT) were excluded. Postoperative FBS at 24-48 hours, 1, 3, 6, and 12 months, and then yearly after the transplantation were performed. RESULTS: A total of 76 LTx cases (75 recipients) were analyzed. The mean age of the recipients was 49.55 years (range, 18-71 years), and 38 (49.4%) were male. Twenty-one out of 76 cases (27.6%) experienced early anastomotic complications, and 12 (15.8%) presented late anastomotic complications. The early anastomotic airway complications presented in various forms: stenosis, 1 case; narrowing, 1; necrosis & dehiscence, 3; fistula, 4; granulation, 10; and infection, 2. Late complications almost entirely presented in the form of bronchial stenosis; five recipients showed stenosis at the anastomosis site, and one of them showed improvement after ballooning. Five others were found to have stenosis at the bronchus intermedius, distal to the anastomosis site. Three of these patients showed improvement after ballooning or bronchoplasty. CONCLUSION: By serial surveillance via FBS after LTx, we detected anastomotic airway complications in 42.9% of cases, which were successfully managed with improved clinical outcomes.
Adolescent ; Adult ; Aged ; Analysis of Variance ; Anastomosis, Surgical/*adverse effects/methods ; Bronchi/blood supply/physiopathology/*surgery ; Bronchial Diseases/epidemiology/*etiology/physiopathology ; Bronchoscopy ; Female ; Humans ; Incidence ; *Lung Transplantation ; Male ; Middle Aged ; Postoperative Complications/epidemiology/*etiology/physiopathology ; Prevalence ; Republic of Korea/epidemiology ; Retrospective Studies ; Treatment Outcome

OBJECTIVEBecause the traditional loop of breathing control and regulation effect on blood circulation, there was rare study of pulmonary vein capacity. We need a noninvasive and accurate pulmonary vascular capacity measurement and analysis method.

METHODSTwelve normal volunteers were performed a total lung CT scan, image data analysis processing by computer software, the whole lungs from the apex to the base of lung with 40-50 layers by hand-cut, the connection between adjacent layers automatically by a computer simulation, the full pulmonary vascular (≥ 0.6 mm) were treated by high-accuracy three-dimensional imaging technology after removing the interference, and then calculate the whole lung and pulmonary vascular.

RESULTSThe whole lung of the 12 normal volunteers from the apex to the base of lung CT scan image layers was 530 ± 98 (range, 431-841). The total capacity of lung and pulmonary vascular blood was 3705 ± 857 (range, 2398-5383) ml, and the total volume of the pulmonary vascular blood was 125 ± 32 (range, 94-201) ml. The pulmonary vein vascular blood volume was 63 ± 16 (range, 47-100) ml.

CONCLUSIONThe method of measuring the three-dimensional imaging of pulmonary vascular capacity by analyzing lung CT scan data is available and accurate.

Computer Simulation ; Healthy Volunteers ; Humans ; Image Processing, Computer-Assisted ; Lung ; blood supply ; Tomography, X-Ray Computed